Sunday, April 27, 2014

CTC Concentration and Cancer

Joseph and I are looking at the correlation between circulatory tumor cell (CTC) concentration in the circulatory system in individuals with metastatic cancer with cancer progression. Seeing as how the circulatory system is the manner through which nutrients are transported throughout a body, it is a potential manner that cancerous cells may metastasize and reach extremities in the organism that it would not have otherwise localized to. Seeing this correlation between the metastasis of an otherwise “pinpoint” cancer that would have been localized solely to one general region to cancer cell concentration in the bloodstream is a promising part of current cancer research and may lead to possible future advancements in monitoring cancer growth by analyzing CTC presence.

CTC and Breast Cancer

One of the articles that I thought was perhaps the most interesting and pertinent was Significance of Circulating Tumor Cells Detected by the CellSearch System in Patients with Metastatic Breast Colorectal and Prostate Cancer . It addressed the three trials that were conducted in clinical centers in the United States, The Netherlands, and the United Kingdom. The trials were ran on a sample consisting of 177 metastatic breast cancer (MBC), 430 metastatic colorectal cancer (MCRC), and 231 metastatic prostate cancer (MPC) patients. The procedure itself involved taking 7.5 ml blood samples from said patients and the patients themselves were monitored over the course of 36 months.   

The data from the previously mentioned trials were summarized in Kaplan-Meier plots, a manner of data representation that we learned about in the first weeks of this class. Attached below is a Kaplan-Meier plot representative of the correlation between the two defined CTC states and survival in the breast cancer patients (Ref. 1).

This Kaplan-Meier plot suggests that those who had a favorable (lower) CTC count in their blood, in general, had a higher probability of survival than those who were detected to have an unfavorable (higher) CTC count in their blood sample. Something that should also be addressed is the manner that "favorable" and "unfavorable" were defined in terms of CTC count. In this study, the cutoff value for what was considered unfavorable were those who had at least 5 CTC in the 7.5 mL sample of blood. I believe that this in itself is a questionable measure, because this manner of stratification is under a definition that isn't explicitly universal. The fact that definitions may vary in different studies could give rise to potentially very different results. There is the possibility that there is no specific cutoff for these two categories, but rather that the CTC state is best determined through a different type of scaling

Though the data appears to be very convincing, I believe that the data itself wouldn’t be this uniform if the sample had consisted of more patients or different methods of analysis. As mentioned in Dr. D. Mavroudis’s article, there are multiple detection methods when detecting CTCs. The manner of analysis that was implemented was the CellSearch system, however something I noticed was that the study involved the implementation of 4',6-diamidino-2-phenylindole (DAPI) in defining CTCs in the bloodstream. DAPI serves as a manner to analyze cells by giving them a blue fluorescent appearance however; something that I believe could’ve possibly affected the representation of DAPI+ cells is the presence of other possible binding sites to DAPI within the blood sample. However, seeing as how this study went through multiple precautions to limit the effects of confounding variables, such as including the assessment of the lack of CD45 and the expression of CK-PE within the defined CTCs, they effectively narrowed this margin of error.

The Future of CTC Analysis

It is clear that research up to this point in time pushes towards the belief that CTCs hold much potential and may one day become an innovating way to monitor cancer cell growth in terms of its ability to metastasize (Ref. 2). As stated in the article, Circulating cancer cells, CTC phenotyping and profiling may one day become a manner to perform real-time tumor biopsy for individualized targeted therapies.

There are, however, as with many other areas in cancer research, so many variables to consider that might offset the efficiency and reliability of these results to justify implementation. Just the many different types of cancers alone introduces the possibility of each acting different in terms of its effect on CTC in a body, and this is only further complicated when one considers the multiple forms of analysis. Additionally,  I believe that it would be difficult to make a generalization about monitoring a disease that is largely “tailored” to the individual.

I realize this post was largely focused on the methods in terms of CTC analysis, however in my next blog post I intend on addressing additional test results from other studies concerning CTC concentration and cancer growth.

Mavroudis, D. "Circulating Cancer Cells." Annals of Oncology 21.Supplement 7 (2010): vii95-vii100. Web.

Miller, M. Craig, Gerald V. Doyle, and Leon W. M. M. Terstappen. "Significance of Circulating Tumor Cells Detected by the CellSearch System in Patients with Metastatic Breast Colorectal and Prostate Cancer." Journal of Oncology 2010 (2010): 1-8.